117 research outputs found
Making it Through: From Start to Finish… Faculty and Student Co-authorship Process
Research Questions: RQ1: What is the process of co-authoring a writing project between professors and students? RQ2: What are professor’s perceptions of co-authoring a writing project with college students? RQ3: What are student’s perceptions of co-authoring a writing project with a professor? RQ4: What communication processes are involved in student faculty co-authorship?
Method: The qualitative method of data collection was utilized for this study. The researchers conducted two focus groups and seven face to face interviews with different subjects, professors and students. This study was conducted at a university in the Pacific Northwest
The synthesis of novel chromogenic enzyme substrates for detection of bacterial glycosidases and their applications in diagnostic microbiology
The preparation and evaluation of chromogenic substrates for detecting bacterial glycosidase enzymes is reported. These substrates are monoglycoside derivatives of the metal chelators catechol, 2,3-dihydroxynaphthalene (DHN) and 6,7-dibromo-2,3-dihydroxynaphthalene (6,7-dibromo-DHN). When hydrolysed by appropriate bacterial enzymes these substrates produced coloured chelates in the presence of ammonium iron(III) citrate, thus enabling bacterial detection. A β-D-riboside of DHN and a β-D-glucuronide derivative of 6,7-dibromo-DHN were particularly effective for the detection of S. aureus and E. coli respectively
Safety of Repeated Open-Label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis:Results from Three Clinical Trials
OBJECTIVES:To investigate the safety of ofatumumab retreatment in rheumatoid arthritis. METHODS:Patients with active rheumatoid arthritis participating in two phase III trials (OFA110635 and OFA110634) and a phase II extension trial (OFA111752) received individualised open-label ofatumumab retreatment (700 mg X 2 intravenous infusions two weeks apart) ≥24 weeks following the first course and ≥16 weeks following further courses. Retreatment required evidence of clinical response followed by disease relapse. These studies were prematurely terminated by the sponsor to refocus development on subcutaneous delivery. Due to differences in study designs and populations, data are summarised separately for each study. RESULTS:483 patients (243, 148 and 92 in OFA110635, OFA110634 and OFA111752 respectively) received up to 7 treatment courses of intravenous ofatumumab; cumulative duration of exposure was 463, 182 and 175 patient-years, respectively. Mean time between courses was 17-47 weeks. Ofatumumab induced a profound depletion of peripheral B-lymphocytes. Retreated patients derived benefit based on improvement in DAS28. Adverse events were reported for 93% (226/243), 91% (134/148) and 76% (70/92), serious adverse events for 18% (44/243), 20% (30/148) and 12% (11/92) and serious infections for 3% (8/243), 5% (7/148) and 1% (1/92) of patients in OFA110635, OFA110634 and OFA111752, respectively. The most common adverse events were infusion-related reactions during the first infusion of the first course (48-79%); serious infusion-related reactions were rare (<1% [1/243], 5% [8/148], and 1% [1/92] of patients). Two deaths occurred (fulminant hepatitis B virus infection and interstitial lung disease). CONCLUSIONS:Ofatumumab was generally well tolerated with no evidence of increased safety risks with multiple retreatments. Serious infections were uncommon and did not increase over time. TRIAL REGISTRATION:ClinicalTrials.gov 110635 ClinicalTrials.gov 110634 ClinicalTrials.gov 111752
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Voice hearers’ experiences of the Making Sense of Voices in an NHS setting
The Making Sense of Voices (MsV) approach (Romme & Escher, 2000) has become established within large sections of the voice hearing community, as well as being adopted by some professional mental health workers. However, there has been limited research to assess this intervention. A recent case series using the MsV approach (Steel et al., 2019) reported promising results across a number of standardised outcome measures. The current study reports on the voice hearers’ experience of having received the MsV intervention, through the use of ‘exit interviews’ conducted as part of the case series. Individual participants’ experiences indicated a range of reactions to the intervention. Positive outcomes appeared to relate to a better understanding of voice hearing experiences and a greater sense of control over voices. Not all participants reported a positive experience of communicating with their voices. Outcomes are discussed within the context of potential common and distinct ‘ingredients’ of the MsV approach, compared to other approaches to working with distressing voices
Assessing the accuracy of free automated plant identification applications
1. Widely available and inexpensive mobile phone applications offer users, whether professional ecologists or interested amateurs, the potential for simple and rapid automated identification of species, without the need to use field guides and identification keys. The increasing accuracy of machine learning is well established, but it is currently unclear if, and under what circumstances, free-to-use mobile phone applications are accurate for identifying plants to species level in real-world field conditions.
2. We test five popular and free identification applications for plants using 857 professionally identified images of 277 species from 204 genera. Across all applications, 85% of images were identified correctly in the top five suggestions, and 69% were correct with the first suggestion. Plant type (woody, forbs, grasses, rushes/sedges, ferns/horsetails) was a significant determinant of identification performance for each application. For some applications, image saliency was also important; exposure and focus were not significant.
3. Applications performed well, with at least one of the three best-performing applications identifying 96% of images correctly as their first suggestion. We conclude that, subject to some caveats, free phone-based plant identification applications are valid and useful tools for those wanting rapid identification and for anyone wanting to engage with the natural world
Validation of the World Health Organization Tool for Situational Analysis to Assess Emergency and Essential Surgical Care at District Hospitals in Ghana
The World Health Organization (WHO) Tool for Situational Analysis to Assess Emergency and Essential Surgical Care (hereafter called the WHO Tool) has been used in more than 25 countries and is the largest effort to assess surgical care in the world. However, it has not yet been independently validated. Test–retest reliability is one way to validate the degree to which tests instruments are free from random error. The aim of the present field study was to determine the test–retest reliability of the WHO Tool.
The WHO Tool was mailed to 10 district hospitals in Ghana. Written instructions were provided along with a letter from the Ghana Health Services requesting the hospital administrator to complete the survey tool. After ensuring delivery and completion of the forms, the study team readministered the WHO Tool at the time of an on-site visit less than 1 month later. The results of the two tests were compared to calculate kappa statistics for each of the 152 questions in the WHO Tool. The kappa statistic is a statistical measure of the degree of agreement above what would be expected based on chance alone.
Ten hospitals were surveyed twice over a short interval (i.e., less than 1 month). Weighted and unweighted kappa statistics were calculated for 152 questions. The median unweighted kappa for the entire survey was 0.43 (interquartile range 0–0.84). The infrastructure section (24 questions) had a median kappa of 0.81; the human resources section (13 questions) had a median kappa of 0.77; the surgical procedures section (67 questions) had a median kappa of 0.00; and the emergency surgical equipment section (48 questions) had a median kappa of 0.81.
Hospital capacity survey questions related to infrastructure characteristics had high reliability. However, questions related to process of care had poor reliability and may benefit from supplemental data gathered by direct observation. Limitations to the study include the small sample size: 10 district hospitals in a single country. Consistent and high correlations calculated from the field testing within the present analysis suggest that the WHO Tool for Situational Analysis is a reliable tool where it measures structure and setting, but it should be revised for measuring process of care
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Making sense of voices: a case series
The current evidence-base for the psychological treatment of distressing voices indicates the need for further clinical development. The Maastricht approach (also known as Making Sense of Voices) is popular within sections of the Hearing Voices Movement, but its clinical effectiveness has not been systematically evaluated. The aim of the approach is to develop a better understanding of the role of the voice, in part through opening a dialogue between the voice hearer and the voice. The current study was a (N=15) case series adopting a concurrent multiple baseline design. The Maastricht approach was offered for up to 9-months. The main outcome, weekly voice-related distress ratings, was not statistically significant during intervention or follow-up, although the effect size was in the moderate range. The PSYRATS Hallucination scale was associated with a large effect size both at the end of treatment, and after a 3-month follow-up period, although again the effect did not reach statistical significance. The results suggest further evaluation of the approach is warranted. However, given the large variance in individual participant outcome, it may be that a better understanding of response profiles is required before conducting a definitive randomised controlled trial
The ASCEND study: protocol for a feasibility study to evaluate an early social communication intervention for young children with Down syndrome
Background
Down syndrome is the most common cause of learning disability, affecting approximately 1 in every 700 babies. Children with Down syndrome have particular difficulties with speech and language. This makes it challenging for them to participate fully in life, access healthcare services and educational opportunities. Improving the language skills of young children with Down syndrome is vital for their future social and emotional well-being and behaviour, and consequently contribution to society. As Down syndrome is detected before or at birth, we can provide support from early on. There are currently no standard interventions for improving the language skills of children with Down syndrome under the age of 36 months. Evidence suggests that early parent-based interventions may be effective in improving language outcomes. In partnership with parents and speech and language therapists, we have co-developed an intervention focusing on early social communication skills and our preliminary work shows that it can lead to better language in children with Down syndrome. Our aim is to carry out a feasibility study which will inform a future pilot/full trial to test whether the intervention is effective in improving language skills before children with Down syndrome start school.
Methods
This is a two-arm feasibility randomised controlled trial (RCT), with 1:1 randomisation stratified by trial site comparing the intervention (plus standard NHS speech and language therapy) with no intervention (standard NHS speech and language therapy only). We aim to recruit between 25 and 30 children with Down syndrome aged between 11 and 36 months. Sites are defined by the geographical boundaries of three National Health Service (NHS) Trusts. Recruitment is from NHS Speech and Language Therapist caseloads within the 3 Trusts, and self-referral. In the intervention arm, parents/guardians will receive brief training on the parent-based intervention and a manual to follow with their child for 10 weeks. The children’s language and early communication skills and family health outcomes will be assessed by a blinded assessor at baseline, post-intervention and 6 month follow-up. Questionnaire and semi-structured interviews will explore the acceptability of the intervention to parents and SLTs.
Discussion
The feasibility study’s outcomes will determine whether it would be viable to progress to a full-trial and whether adjustments need to made to the procedures, data collection methods, intervention delivery and the intensity of support needed. We want to assess whether our early intervention can be delivered and rolled out through NHS Speech and Language Therapy (SLT) Services. We anticipate that NHS SLT Services will need to make ongoing changes due to the COVID-19 pandemic, so it is likely that we will need to make adjustments for the definitive trial. We will also calculate descriptive statistics of the language outcome measure which we will use for any future sample size calculation
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Accuracy of UK Rapid Test Consortium (UK-RTC) "AbC-19 Rapid Test" for detection of previous SARS-CoV-2 infection in key workers: test accuracy study.
OBJECTIVE: To assess the accuracy of the AbC-19 Rapid Test lateral flow immunoassay for the detection of previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN: Test accuracy study. SETTING: Laboratory based evaluation. PARTICIPANTS: 2847 key workers (healthcare staff, fire and rescue officers, and police officers) in England in June 2020 (268 with a previous polymerase chain reaction (PCR) positive result (median 63 days previously), 2579 with unknown previous infection status); and 1995 pre-pandemic blood donors. MAIN OUTCOME MEASURES: AbC-19 sensitivity and specificity, estimated using known negative (pre-pandemic) and known positive (PCR confirmed) samples as reference standards and secondly using the Roche Elecsys anti-nucleoprotein assay, a highly sensitive laboratory immunoassay, as a reference standard in samples from key workers. RESULTS: Test result bands were often weak, with positive/negative discordance by three trained laboratory staff for 3.9% of devices. Using consensus readings, for known positive and negative samples sensitivity was 92.5% (95% confidence interval 88.8% to 95.1%) and specificity was 97.9% (97.2% to 98.4%). Using an immunoassay reference standard, sensitivity was 94.2% (90.7% to 96.5%) among PCR confirmed cases but 84.7% (80.6% to 88.1%) among other people with antibodies. This is consistent with AbC-19 being more sensitive when antibody concentrations are higher, as people with PCR confirmation tended to have more severe disease whereas only 62% (218/354) of seropositive participants had had symptoms. If 1 million key workers were tested with AbC-19 and 10% had actually been previously infected, 84 700 true positive and 18 900 false positive results would be projected. The probability that a positive result was correct would be 81.7% (76.8% to 85.8%). CONCLUSIONS: AbC-19 sensitivity was lower among unselected populations than among PCR confirmed cases of SARS-CoV-2, highlighting the scope for overestimation of assay performance in studies involving only PCR confirmed cases, owing to "spectrum bias." Assuming that 10% of the tested population have had SARS-CoV-2 infection, around one in five key workers testing positive with AbC-19 would be false positives. STUDY REGISTRATION: ISRCTN 56609224.The study was commissioned by the UK Government’s Department of Health and Social Care. It was funded and implemented by Public Health England, supported by the NIHR Clinical Research Network (CRN) Portfolio. The Department of Health and Social Care received a report containing these data on 10/9/2020, but had no role in the study design, data collection, analysis, interpretation of results, writing of the manuscript, or the decision to publish. DW acknowledges support from the NIHR Health Protection Research Unit in Genomics and Data Enabling at the University of Warwick. HEJ, AEA, MH and IO acknowledge support from the NIHR Health Protection Research Unit in Behavioural Science and Evaluation at University of Bristol. STP is supported by an NIHR Career Development Fellowship (CDF-2016-09-018). Participants in the COMPARE study were recruited with the active collaboration of NHS Blood and Transplant (NHSBT) England (www.nhsbt.nhs.uk). Funding for COMPARE was provided by NHSBT and the NIHR Blood and Transplant Research Unit (BTRU) in Donor Health and Genomics (NIHR BTRU-2014-10024). The academic coordinating centre for COMPARE was supported by core funding from: NIHR BTRU, UK Medical Research Council (MR/L003120/1), British Heart Foundation (RG/13/13/30194) and the NIHR [Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust]. This work was supported by Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Division), Public Health Agency (Northern Ireland), British Heart Foundation and Wellcome. JD holds a British Heart Foundation Professorship and a National Institute for Health Research Senior Investigator Award. The views expressed are those of the author(s) and not necessarily those of the NHS, NIHR or the Department of Health and Social Care
Alpha kinase 3 signaling at the M-band maintains sarcomere integrity and proteostasis in striated muscle
Muscle contraction is driven by the molecular machinery of the sarcomere. As phosphorylation is a critical regulator of muscle function, the identification of regulatory kinases is important for understanding sarcomere biology. Pathogenic variants in alpha kinase 3 (ALPK3) cause cardiomyopathy and musculoskeletal disease, but little is known about this atypical kinase. Here we show that ALPK3 is an essential component of the M-band of the sarcomere and define the ALPK3-dependent phosphoproteome. ALPK3 deficiency impaired contractility both in human cardiac organoids and in the hearts of mice harboring a pathogenic truncating Alpk3 variant. ALPK3-dependent phosphopeptides were enriched for sarcomeric components of the M-band and the ubiquitin-binding protein sequestosome-1 (SQSTM1) (also known as p62). Analysis of the ALPK3 interactome confirmed binding to M-band proteins including SQSTM1. In human pluripotent stem cell-derived cardiomyocytes modeling cardiomyopathic ALPK3 mutations, sarcomeric organization and M-band localization of SQSTM1 were abnormal suggesting that this mechanism may underly disease pathogenesis
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